We have chosen some related facets of this general problem for study at the present time and have selected the appropriate preparation and experimental method to provide answers to the fundamental problem. The nature of the processes by which hydrophilic and hydrophobic solutes traverse cell membranes and the effect of mercury compounds and other sulfhydryl and amino reactive groups on these processes will be investigated. The effect on these processes of important physical parameters such as temperature, pH and ionic strength will also be studied. In addition, we will modify chemically the membrane structure in an attempt to gain a better understanding of the role of its various constituents in particular cholesterol in the regulation of solute permeability. We expect to gain basic information about the interaction of permeating nonelectrolytes with varying chemical composition, reactive groups, hydrogen binding and physical properties with membrane. Furthermore, we seek to understand the toxic effect of mercury compounds and the role of various chemical groups in biological membranes.